Little attention has been focused on the immunological response of an organ recipient against the transplant, due largely to lack of suitable methodology. The Colony Inhibition test of the Hellstroms is uniquely suited to detect the presence or absence of recipient cellular immunity against donor target cells and also to reveal the presence or absence of serum blocking factors. Utilizing this test we have studied 36 patients who received renal homografts at the University of Washington over a 38-month period. The results to date show an early induction of lymphocyte reactivity, presence of serum blocking factors in those with the most benign clinical courses, and late in the course after operation, a reversion of the lymphocytes to a state of non- reactivity to donor fibroblasts. These findings appear to be related only to the presence of the allograft and did not correlate with the recipient's original disease, histocompatibility match or ischemic intervals. The only variable which could not be altered at will was the immunosuppressive regimen. We propose in this project to extend these studies to genetically defined, tissue-matched dogs and systematically investigate the development of recipient cellular immunity, serum blocking factors and the relationships of the development of host-graft non-reactivity to immunosuppression and clinical outcome in pairs of animals bearing renal homografts.